We reported on a unique complement regulatory component sgp120 in J. Biol. Chem, 264:2283-2291, 1989. This plasma protein co-isolates with the second component of human complement (C2) on "C4b"-Sepharose but only at 3-5% yield (sgp120-A). The presence in sgp120 of the O-linked carbohydrate galactose was used to develop an affinity isolation procedure. The capacity of sgp120 to bind to the galactosyl-specific lectin, Jacalin was used in part to purity sgp120-l (non-C4b binding form) containing <10% sgp120-A (subsequently recovered by use of "C4b"-Sepharose). Although the two forms are immunochemically indistinguishable by double diffusion analysis, produce similar fragments on kallikrein digestion and have identical N-terminal amino-acid sequences, by a number of criteria these two forms are distinct and in particular sgp120-A possess most of the described functional activity. Dose-responsive inhibition by sgp120 of the Classical Complement Pathway has been confirmed. Sgp120-A demonstrates up to 10 times the specific inhibitory capacity as found for sgp120-l. Data support inhibition of the C3 convertase, EAC14b2a, by competition with C1 and C2 for a site or sites on bound C4b. Sgp120-A does not compete with C4 for binding to its acceptor on the cell surface. We have fully sequenced the initially identified and isolated clone that produces a fusion protein detectable by monospecific antibody to sgp120. The partial deduced sequence contained the N-terminal peptide sequence derived from a C-terminal 35 kDa fragment derived from sgp120-A. We have also identified and fully sequenced three additional sgp120 clones that, although not full length, contain the 16 amino acid sequence determined by N-terminal analysis of the 25 kDa peptide derived from the 85 kDa peptide by kallikrein digestion of sgp120-A. The deduced amino acid sequences for these sgp120 clones are not present in the current protein database containing 70,000 sequences (January 91) and confirms our report of sgp120 as a new plasma protein.